Biology subjects

Gruber, T.

Publications and source records attributed to Gruber, T..

26 records · Page 2Linked to original sources

bioRxiv2021

Brain endothelial antigen presentation detains CD8+ T cells at the blood-brain barrier leading to its breakdown

Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system (CNS) are early hallmarks of multiple sclerosis (MS). High numbers of CD8+ T cells are found in MS lesions and antigen (Ag)-presentation at the BBB was proposed to promote CD8+ T-cell entry into the CNS. Employing live cell imaging and primary mouse brain microvascular endothelial cells (pMBMECs) as in vitro model of the BBB and a mouse model of CNS autoimmunity, we here show that pMBMECs process and present antigens leading to effector CD8+ T-cell differentiation. Under physiological flow, endothelial Ag-presentation prohibited CD8+ T-cell crawling and diapedesis leading to pMBMEC apoptosis. Reduced motility of Ag-specific CD8+ T cells was also observed in CNS microvessels in neuroinflammation in vivo. Luminal MHC class I Ag-presentation at the BBB thus prohibits CD8+ T-cell entry into the CNS and rather triggers CD8+ T cell mediated focal BBB breakdown.

immunology↗

bioRxiv2020

Human temporal voice areas are sensitive to chimpanzee vocalizations

Withdrawal StatementThe authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2025/677258. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi: 10.1101/2025.09.19.677258

neuroscience↗

bioRxiv2020

Brain activation lateralization in monkeys (Papio Anubis) following asymmetric motor and auditory stimulations through functional Near Infrared Spectroscopy

Hemispheric asymmetries have long been seen as characterizing the human brain; yet, an increasing number of reports suggest the presence of such brain asymmetries in our closest primate relatives. However, most available data in non-human primates have so far been acquired as part of neurostructural approaches such as MRI, while comparative data in humans are often dynamically acquired as part of neurofunctional studies. In the present exploratory study in baboons (Papio Anubis), we tested whether brain lateralization could be recorded non-invasively using a functional Near-Infrared Spectroscopy (fNIRS) device in two contexts: motor and auditory passive stimulations. Under light propofol anaesthesia monitoring, three adult female baboons were exposed to a series of (1) left-versus right-arm passive movement stimulations; and (2) left-versus right-ear versus stereo auditory stimulations while recording fNIRS signals in the related brain areas (i.e., motor central sulcus and superior temporal cortices respectively). For the motor condition our results show that left-arm versus right-arm stimulations induced typical contralateral difference in hemispheric activation asymmetries in the three subjects for all three channels. For the auditory condition, we also revealed typical human-like patterns of hemispheric asymmetries in one subject for all three channels, namely (1) typical contralateral differences in hemispheric asymmetry between left-ear versus right-ear stimulations, and (2) a rightward asymmetry for stereo stimulations. Overall, our findings support the use of fNIRS to investigate brain processing in non-human primates from a functional perspective, opening the way for the development of non-invasive procedures in non-human primate brain research.

neuroscience↗

bioRxiv2020

Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis

Reorganization of the extracellular matrix is a prerequisite for healthy adipose tissue expansion, whereas fibrosis is a key feature of adipose dysfunction and inflammation. However, very little is known about the direct effects of impaired cell-matrix interaction in adipocyte function and insulin sensitivity. Using adipose selective deletion of {beta}1 integrin (Itgb1adipo-cre) and Kindlin-2 (Kind2adipo-cre), we demonstrate here that active {beta}1 and {beta}3 integrins directly interact with the insulin receptor to regulate white adipocyte insulin action and systemic metabolism. Consequently, loss of adipose integrin activity, similar to loss of adipose insulin receptors, results in lipodystrophy and systemic insulin resistance. Conversely, we find that brown adipose tissue of Kind2adipo-cre and Itgb1adipo-cre mice is chronically hyperactivated, and has increased substrate delivery, reduced endothelial basement membrane thickness, and increased endothelial vesicular transport. Thus, we establish integrin-extracellular matrix interactions as key regulators of white and brown adipose tissue function and whole body metabolism.

physiology↗

bioRxiv2019

Ecological and dietary differences between Ugandan chimpanzee communities with possible implications on tool use

Some East African chimpanzee (Pan troglodytes schweinfurthii) communities, such as the Sonso chimpanzees, display an unusually limited range of tool-use, but it remains unclear whether this is due to ecological and/or cultural factors. Information on ecological conditions and the diet of the Sonso chimpanzees in relation to neighbouring communities is needed. Here, we studied three adjacent communities in Budongo Forest (Sonso, Waibira, and Kamira), and the presumed core area of an undescribed community (Mwera), in the neighbouring Bugoma Forest. Through line-transects, we investigated (i) whether there were differences in food diversity and abundance between the communities home ranges; (ii) whether the home ranges differed in abundance of sticks and insect nests; and (iii) whether Sonso and Mwera chimpanzees differed in their diet (using faecal samples). Across communities, Sonso had the richest food availability and the lowest insect nest abundance. However, food availability in Mwera, Bugoma, was richer than Budongo communities that neighbour the Sonso territory, suggesting that there may be variation within Budongo. Data from faecal samples replicated our direct observations of food availability suggesting that Sonso chimpanzees had a broader diet than Mwera chimpanzees. This difference in foods availability may partially explain the Sonso chimpanzees lack of stick-tool-use, and low levels of insectivory. The tool repertoire of the other communities is currently unknown; however, we make predictions based on our ecological data. More detailed knowledge of small-scale variation in ecology within and between forest habitats may be important to advancing our understanding of the drivers of tool-use.\n\nSIGNIFICANCE STATEMENT - HIGHLIGHTED STUDENT PAPERTo advance our knowledge of the role of ecological factors in the emergence of tool use in chimpanzees, a nuanced understanding of the ecological conditions different chimpanzee communities experience is needed. We studied four Ugandan chimpanzee communities in two forests. One of these communities, Sonso, in the Budongo Forest, is well-known for its restricted range of tool types, including a total absence of stick use. Food diversity and abundance were highest, and stick tool use opportunities (abundance of sticks and insect nests) were lowest for the core-habitat of the Sonso chimpanzees in contrast to the other communities. We argue that ecological factors play a role in their unusual pattern of tool use, and make predictions about the expected types of tool use in the other communities based on their ecology. Thus, our study provides information that may help advance our understanding of how tool use arises under varied socioecological circumstances.

ecology↗

bioRxiv2019

Variable Retention of Differentiation-specific DNA Replication Timing in Human Pediatric Leukemia

Human B-lineage precursor acute lymphoid leukemias (BCP-ALLs) comprise a group of genetically and clinically distinct disease entities with features of differentiation arrest at known stages of normal B-lineage differentiation. We previously showed BCP-ALL cells display unique and clonally heritable DNA-replication timing (RT) programs; i.e., programs describing the variable order of replication of megabase-scale chromosomal units of DNA in different cell types. To determine the extent to which BCP-ALL RT programs mirror or deviate from specific stages of normal human B-cell differentiation, we transplanted immunodeficient mice with quiescent normal human CD34+ cord blood cells and obtained RT signatures of the regenerating B-lineage populations. We then compared these with RT signatures for leukemic cells from a large cohort of BCP-ALL patients. The results identify BCP-ALL subtype-specific features that resemble specific stages of B-cell differentiation and features that appear associated with relapse. These results suggest the genesis of BCP-ALL involves alterations in RT that reflect clinically relevant leukemia-specific genetic and/or epigenetic changes. SUMMARYGenome-wide DNA replication timing profiles of >100 pediatric leukemic samples and normally differentiating human B-lineage cells isolated from xenografted immunodeficient mice were generated. Comparison of these identified potentially clinically relevant features that both match and deviate from the normal profiles.

cancer biology↗

bioRxiv2019

Human discrimination and categorization of emotions in voices: a functional Near-Infrared Spectroscopy (fNIRS) study

Variations of the vocal tone of the voice during speech production, known as prosody, provide information about the emotional state of the speaker. In recent years, functional imaging has suggested a role of both right and left inferior frontal cortices in attentive decoding and cognitive evaluation of emotional cues in human vocalizations. Here, we investigated the suitability of functional Near-Infrared Spectroscopy (fNIRS) to study frontal lateralization of human emotion vocalization processing during explicit and implicit categorization and discrimination. Participants listened to speech-like but semantically meaningless words spoken in a neutral, angry or fearful tone and had to categorize or discriminate them based on their emotional or linguistic content. Behaviorally, participants were faster to discriminate than to categorize and they processed the linguistic content of stimuli faster than their emotional content, while an interaction between condition (emotion/word) and task (discrimination/categorization) influenced accuracy. At the brain level, we found a four-way interaction in the fNIRS signal between condition, task, emotion and channel, highlighting the involvement of the right hemisphere to process fear stimuli, and of both hemispheres to treat anger stimuli. Our results show that fNIRS is suitable to study vocal emotion evaluation in humans, fostering its application to study emotional appraisal.

neuroscience↗

bioRxiv2017

Memory entrainment by visually evoked theta-gamma coupling in the human brain

It is an integral function of the human brain to sample novel information from the environment and to update the internal representation of the external world. The formation of new memories is assumed to be orchestrated by neuronal oscillations, the rhythmic synchronization of neuronal activity within and across cell assemblies. Specifically, successful encoding of novel information is associated with increased theta oscillations (3-8Hz) and theta coupled gamma activity (40-120Hz), and a decrease in alpha oscillations (8-12Hz). However, given the correlative nature of neurophysiological recordings, the causal role of neuronal rhythms in human memory encoding is still unclear. Here, we experimentally enhance the formation of novel memories by a visual brain stimulation at an individually adjusted theta frequency, in contrast to the stimulation at an individual alpha frequency. Critically, the memory entrainment effect by the theta stimulation was not explained by theta power per se, but was driven by visually evoked theta-gamma coupling in wide spread cortical networks. These findings provide first evidence for a functional role of the theta rhythm and the theta-gamma neuronal code in human episodic memory. Yet more strikingly, the entrainment of mnemonic network mechanisms by a simplistic visual stimulation technique provides a proof of concept that internal rhythms align with visual pacemakers, which can entrain complex cognitive functions in the wake human brain.

neuroscience↗